Ivabradine for controlling heart rate in permanent atrial fibrillation: A translational clinical trial.

BACKGROUND: Pharmacological options for rate control in atrial fibrillation are scarce. Ivabradine was postulated to reduce the ventricular rate in this setting. OBJECTIVES: The objectives of this study were to evaluate the mechanism of inhibition of atrioventricular conduction produced by ivabradine and to determine its efficacy and safety in atrial fibrillation. METHODS: The effects of ivabradine on atrioventricular node and ventricular cells were studied by in vitro whole-cell patch-clamp experiments and mathematical simulation of human action potentials. In parallel, a multicenter, randomized, open-label, phase III clinical trial compared ivabradine with digoxin for uncontrolled permanent atrial fibrillation despite ß-blocker or calcium channel blocker treatment. RESULTS: Ivabradine 1 µM inhibited "funny" current and rapidly activating delayed rectifier potassium channel current by 28.9% and 22.8%, respectively (P < .05). The sodium channel current and L-type calcium channel current were reduced only at 10 µM. Ivabradine slowed the firing frequency of a modeled human atrioventricular node action potential by 10.6% and induced a minimal prolongation of ventricular action potential. Thirty-five (51.5%) patients were randomized to ivabradine and 33 (49.5%) to digoxin. The mean daytime heart rate decreased by 11.6 beats/min (-11.5%) in the ivabradine arm (P = .02) vs 19.6 (-20.6%) in the digoxin arm (P < .001), although the noninferiority margin of efficacy was not met (Z = -1.95; P = .97). The primary safety end point occurred in 3 patients (8.6%) on ivabradine and in 8 (24.2%) on digoxin (P = .10). CONCLUSION: Ivabradine produced a moderate rate reduction in patients with permanent atrial fibrillation. The inhibition of funny current in the atrioventricular node seems to be the main mechanism responsible for this reduction. Compared with digoxin, ivabradine was less effective, was better tolerated, and had a similar rate of serious adverse events.

Analysis of Sex-Specific Prostanoid Production Using a Mouse Model of Selective Cyclooxygenase-2 Inhibition.

Background: Prostanoids are a family of lipid mediators formed from arachidonic acid by cyclooxygenase enzymes and serve as biomarkers of vascular function. Prostanoid production may be different in males and females indicating that different therapeutic approaches may be required during disease. Objectives: We examined sex-dependent differences in COX-related metabolites in genetically modified mice that produce a cyclooxygenase-2 (COX2) enzyme containing a tyrosine 385 to phenylalanine (Y385F) mutation. This mutation renders the COX2 enzyme unable to form a key intermediate radical required for complete arachidonic acid metabolism and provides a model of selective COX2 inhibition. Design and Methods: Mice heterozygous for the Y385F mutation in COX2 were mated to produce cohorts of wild-type, heterozygous, and COX2 mutant mice. We investigated whether the genotype distribution followed Mendelian genetics and studied whether sex-specific differences could be found in certain prostanoid levels measured in peritoneal macrophages and in urinary samples. Results: The inheritance of the COX2 mutation displayed a significant deviation with respect to Mendel's laws of genetics, with a lower-than-expected progeny of weaned COX2 mutant pups. In macrophages, prostaglandin E2 (PGE2) production following lipopolysaccharide (LPS) and interferon gamma (IFNγ) stimulation was COX2-dependent in both males and females, and data indicated that crosstalk between the nitric oxide (NO) and COX2 pathways may be sex specific. We observed significant differences in urinary PGE2 production by male and female COX2 mutant mice, with the loss of COX2 activity in male mice decreasing their ability to produce urinary PGE2. Finally, female mice across all 3 genotypes produced similar levels of urinary thromboxane (measured as 11-dehydro TxB2) at significantly higher levels than males, indicating a sex-related difference that is likely COX1-derived. Conclusions: Our findings clearly demonstrate that sex-related differences in COX-derived metabolites can be observed, and that other pathways (such as the NO pathway) are affected.

Executive summary of outpatient parenteral antimicrobial therapy: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases and the Spanish Domiciliary Hospitalisation Society / Resumen ejecutivo del tratamiento antimicrobiano domiciliario endovenoso: guía de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica y la Sociedad Española de Hospitalización a Domicilio

Outpatient parenteral antimicrobial therapy (OPAT) programmes make it possible to start or complete intravenous antimicrobial therapy for practically any type of infection at home, provided that patient selection is appropriate for the type of OPAT programme available. Although the clinical management of infections in the home setting is comparable in many respects to that offered in conventional hospitalization (selection of antibiotics, duration of treatment, etc.), there are many aspects that are specific to this care modality. It is essential to be aware of them so that OPAT continues to be as safe and effective as inpatient care. The objective of this clinical guideline is therefore to provide evidence- and expert-based recommendations with a view to standardizing clinical practice in this care modality and contribute to a progressive increase in the number of patients who can be cared for and receive intravenous therapy in their own homes

Los programas de tratamiento antibiótico domiciliario endovenoso (TADE) permiten iniciar o completar el tratamiento antimicrobiano por vía endovenosa de prácticamente cualquier tipo de infección en el domicilio, siempre y cuando se realice una selección del paciente acorde al tipo de programa de TADE que se dispone. Aunque hay aspectos del manejo clínico de las infecciones en el domicilio que son superponibles en la mayoría de los casos a la realizada en la hospitalización convencional (selección de la antibioterapia, duración del tratamiento, etc.), existen numerosos aspectos que son específicos de esta modalidad asistencial. Resulta imprescindible conocerlos para que el TADE siga siendo igual de eficaz y seguro que la hospitalización convencional. El objetivo de esta guía clínica es por tanto, proporcionar recomendaciones basadas en la evidencia realizadas por expertos para homogeneizar la práctica clínica de esta modalidad asistencial y contribuir a que se incremente progresivamente el número de pacientes que pueden ser atendidos y recibir tratamiento endovenoso en su propio domicilio

Executive summary of outpatient parenteral antimicrobial therapy: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases and the Spanish Domiciliary Hospitalisation Society.

Outpatient parenteral antimicrobial therapy (OPAT) programmes make it possible to start or complete intravenous antimicrobial therapy for practically any type of infection at home, provided that patient selection is appropriate for the type of OPAT programme available. Although the clinical management of infections in the home setting is comparable in many respects to that offered in conventional hospitalization (selection of antibiotics, duration of treatment, etc.), there are many aspects that are specific to this care modality. It is essential to be aware of them so that OPAT continues to be as safe and effective as inpatient care. The objective of this clinical guideline is therefore to provide evidence- and expert-based recommendations with a view to standardizing clinical practice in this care modality and contribute to a progressive increase in the number of patients who can be cared for and receive intravenous therapy in their own homes.

Exposición de las cardiólogas intervencionistas a radiaciones ionizantes durante el embarazo. ¿Realmente representa un riesgo para el feto? / Radiation exposure to the pregnant interventional cardiologist. Does it really pose a risk to the fetus?

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Beneficios de la natación en el asma / Benefits of swimming in asthma

El asma es una enfermedad crónica e incurable, hasta el día de hoy, que consiste en la inflamación de las vías aéreas. Provoca tos, dolores de pecho y problemas para respirar. Aunque estamos ante una enfermedad incurable, sí que se pueden minimizar y controlar sus síntomas. En este trabajo de revisión se podrá apreciar que la práctica de la natación puede ser muy beneficiosa para que las personas que padecen asma tengan una mejor calidad de vida, no solo por reducir los síntomas de la enfermedad, sino porque aumenta la autoestima de quienes la padecen.

Asthma is, until today, a chronic and incurable disease consisting on inflammation of the airways. It causes coughs, chest pains and trouble breathing. Although we face with an incurable disease, its symptoms can be minimized and controlled. In this review we will see how the practice of swimming is very beneficial for people with asthma to have a better quality of life, not only by reducing the symptoms of asthma but also because it increases the self-esteem of those who suffer from it.

Primer caso de administración de ceftazidima/avibactam en hospitalización a domicilio. Bacteriemia por Klebsiella pneumoniae BLEE multirresistente / First case of ceftazidime/avibactam administration in home care. ESBL producing Klebsiella pneumoniae bacteremia

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Indicadores de calidad asistencial de GeSIDA para la atención de personas infectadas por el VIH/sida asociados a mortalidad e ingreso hospitalario / GeSIDA quality care indicators associated with mortality and hospital admission for the care of persons infected by HIV/AIDS

INTRODUCCIÓN: En 2010 el Grupo Español de Estudio de SIDA (GeSIDA) desarrolló 66 indicadores de calidad asistencial. Nuestro objetivo es determinar cuáles de estos indicadores se asocian a mortalidad y/o ingreso, y realizar una evaluación preliminar de la utilidad de un índice predictor de mortalidad e ingreso. MÉTODOS: Estudio de cohortes retrospectivo realizado en el Hospital Universitario Son Espases. Los pacientes con infección por el virus de la inmunodeficiencia humana incluidos fueron aquellos que iniciaron seguimiento en consultas entre el 1 de enero de2000 y el 31 de diciembre de 2012. Se realizó análisis descriptivo de las variables demográficas y de los indicadores, y un estudio de regresión logística para valorar la asociación entre los indicadores y riesgo de mortalidad/ingreso. Se calcularon índices predictores de mortalidad e ingreso para pacientes en seguimiento y en tratamiento. RESULTADOS: Fueron incluidos 1.944 pacientes (media de edad: 37 años, el 78,8% varones). En el análisis multivariante relativo a mortalidad, los indicadores asociados en pacientes en seguimiento fueron el 7, 16 y 20 y en pacientes en tratamiento se añaden el 35 y 38. En el análisis multivariante relativo a ingreso, los indicadores asociados en pacientes en seguimiento fueron los mismos que para mortalidad, además del 31, y en el grupo de pacientes en tratamiento se asociaban los indicadores 7, 16, 20, 35, 38 y 40. CONCLUSIÓN: Se han identificado varios indicadores de calidad que pueden estar relacionados con ingreso hospitalario y mortalidad. Estos indicadores hacen referencia fundamentalmente al retraso diagnóstico, seguimiento regular, prevención de las infecciones y control de comorbilidades

INTRODUCTION: In 2010, the AIDS Study Group (Grupo de Estudio del SIDA [GESIDA]) developed 66 quality care indicators. The aim of this study is to determine which of these indicators are associated with mortality and hospital admission, and to perform a preliminary assessment of a prediction rule for mortality and hospital admission in patients on treatment and follow-up. METHODS: A retrospective cohort study was conducted in the Hospital Universitario Son Espases (Palma de Mallorca, Spain). Eligible participants were patients with human immunodeficiency syndrome≥18 years old who began follow-up in the Infectious Disease Section between 1 January 2000 and 31 December 2012. A descriptive analysis was performed to evaluate anthropometric variables, and a logistic regression analysis to assess the association between GESIDA indicators and mortality/admission. The mortality probability model was built using logistic regression. RESULTS: A total of 1,944 adults were eligible (median age: 37 years old, 78.8% male). In the multivariate analysis, the quality of care indicators associated with mortality in the follow-up patient group were the items 7, 16 and 20, and in the group of patients on treatment were 7, 16, 20, 35, and 38. The quality of care indicators associated with hospital admissions in the follow-up patients group were the same as those in the mortality analysis, plus number 31. In the treatment group the associated quality of care indicators were items 7, 16, 20, 35, 38, and 40. CONCLUSIONS: Some GeSIDA quality of care indicators were associated with mortality and/or hospital admissions. These indicators are associated with delayed diagnosis, regular monitoring, prevention of infections, and control of comorbidities

[GeSIDA quality care indicators associated with mortality and hospital admission for the care of persons infected by HIV/AIDS]. / Indicadores de calidad asistencial de GeSIDA para la atención de personas infectadas por el VIH/sida asociados a mortalidad e ingreso hospitalario.

INTRODUCTION: In 2010, the AIDS Study Group (Grupo de Estudio del SIDA [GESIDA]) developed 66 quality care indicators. The aim of this study is to determine which of these indicators are associated with mortality and hospital admission, and to perform a preliminary assessment of a prediction rule for mortality and hospital admission in patients on treatment and follow-up. METHODS: A retrospective cohort study was conducted in the Hospital Universitario Son Espases (Palma de Mallorca, Spain). Eligible participants were patients with human immunodeficiency syndrome≥18 years old who began follow-up in the Infectious Disease Section between 1 January 2000 and 31 December 2012. A descriptive analysis was performed to evaluate anthropometric variables, and a logistic regression analysis to assess the association between GESIDA indicators and mortality/admission. The mortality probability model was built using logistic regression. RESULTS: A total of 1,944 adults were eligible (median age: 37 years old, 78.8% male). In the multivariate analysis, the quality of care indicators associated with mortality in the follow-up patient group were the items 7, 16 and 20, and in the group of patients on treatment were 7, 16, 20, 35, and 38. The quality of care indicators associated with hospital admissions in the follow-up patients group were the same as those in the mortality analysis, plus number 31. In the treatment group the associated quality of care indicators were items 7, 16, 20, 35, 38, and 40. CONCLUSIONS: Some GeSIDA quality of care indicators were associated with mortality and/or hospital admissions. These indicators are associated with delayed diagnosis, regular monitoring, prevention of infections, and control of comorbidities.

Cavo-tricuspid isthmus radiofrequency ablation using a novel remote navigation catheter system in patients with typical atrial flutter.

AIMS: A new remote catheter system (AMIGO™ Remote Catheter System) compatible with conventional ablation catheters is now commercially available but no data about its performance in clinical use during ablation have been reported. This study evaluates the feasibility, efficacy, and safety of cavo-tricuspid isthmus (CTI) ablation with this system in patients with typical atrial flutter (AFl). METHODS AND RESULTS: Sixty patients with typical AFl underwent CTI ablation using the new remote catheter navigation system with 8 mm tip or irrigated catheters in three centres following each centre's routine practice. The endpoint was stable bidirectional CTI block. CTI ablation was successful in 98% of patients. Ablation was completed manually in one patient. The overall procedure, fluoroscopy, and radiofrequency times (median ± standard deviation, range) were 123 ± 42 (50-250), 24 ± 13 (3-82), and 10 ± 8 (1.17-43.3) min, respectively. Three patients had vascular complications not requiring surgical intervention. There were no complications related to the remote catheter manipulation system. CONCLUSION: Cavo-tricuspid isthmus ablation for typical AFl can be safely and effectively performed with the AMIGO™. The learning curve seems to be short even for physicians with limited ablation experience.

Discovery of novel orally bioavailable oxaborole 6-carboxamides that demonstrate cure in a murine model of late-stage central nervous system african trypanosomiasis.

We report the discovery of novel boron-containing molecules, exemplified by N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-trifluoromethylbenzamide (AN3520) and 4-fluoro-N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-trifluoromethylbenzamide (SCYX-6759), as potent compounds against Trypanosoma brucei in vitro, including the two subspecies responsible for human disease T. b. rhodesiense and T. b. gambiense. These oxaborole carboxamides cured stage 1 (hemolymphatic) trypanosomiasis infection in mice when administered orally at 2.5 to 10 mg/kg of body weight for 4 consecutive days. In stage 2 disease (central nervous system [CNS] involvement), mice infected with T. b. brucei were cured when AN3520 or SCYX-6759 were administered intraperitoneally or orally (50 mg/kg) twice daily for 7 days. Oxaborole-treated animals did not exhibit gross signs of compound-related acute or subchronic toxicity. Metabolism and pharmacokinetic studies in several species, including nonhuman primates, demonstrate that both SCYX-6759 and AN3520 are low-clearance compounds. Both compounds were well absorbed following oral dosing in multiple species and also demonstrated the ability to cross the blood-brain barrier with no evidence of interaction with the P-glycoprotein transporter. Overall, SCYX-6759 demonstrated superior pharmacokinetics, and this was reflected in better efficacy against stage 2 disease in the mouse model. On the whole, oxaboroles demonstrate potent activity against all T. brucei subspecies, excellent physicochemical profiles, in vitro metabolic stability, a low potential for CYP450 inhibition, a lack of active efflux by the P-glycoprotein transporter, and high permeability. These properties strongly suggest that these novel chemical entities are suitable leads for the development of new and effective orally administered treatments for human African trypanosomiasis.